Phar 341 - Cholinergic Agonists

Front 1

Define: cholinergic agonist

Back 1

A drug which activates muscarinic and/or nicotinic acetylcholine receptors.

Front 2

Define: cholinergic antagonist

Back 2

A drug which blocks muscarinic and/or nicotinic acetylcholine receptors.

Front 3

Define: parasympathomimetic

Back 3

A drug which activates the PNS.

Front 4

Define: parasympatholytic

Back 4

A drug that blocks the actions of the PNS.

Front 5

Define: non-selective direct-acting cholinergic agonist

Back 5

A drug that activates both nicotinic and muscarinic receptors.

Front 6

At which dose does Acetylcholine activate nicotinic and muscarinic receptors?

Back 6

Low dose - muscarinic

High dose - nicotinic

Note: nicotinic effects only occur with high dose, or when co-administered with muscarinic blocker.

Front 7

What is the duration of action of acetylcholine? How is it metabolized?

Back 7

It has a short duration.

Is metabolized by acetylcholinesterases in blood.

Front 8

What's the difference between a fish and a guitar?

Back 8

You can't tuna fish.

Front 9

What are muscarinic actions of ACh on the cardiovascular system? (3)

Back 9

1. Vasodilation

2. Decreased inotropy (force)

3. Decreased chronotropy (speed)

Front 10

For the PNS, what may occur to the cardiovascular system when ACh is administered intravenously?

Back 10

Hypotension (low BP) and reflex tachycardia (increase HR).

Front 11

For the PNS, what occurs to the respiratory system when ACh is released to muscarinic receptors?

Back 11

Bronchoconstriction and increased secretions.

Front 12

For the PNS, what occurs to the GI when ACh is released to muscarinic receptors?

Back 12

Increased motility and secretions, though usually not observed because the drug is so short acting.

Front 13

Which effects of injected ACh would not be due to the PNS?

Back 13

1. Sweating

2. Vasodilation/ hyptension

3. Increased inotropy

Front 14

If we intravenously inject ACh with a muscarinic blocker, what is the effect on blood pressure?

Back 14

Increased blood pressure.

Muscarinic receptor antagonist blocks vasodilation, decreased inotropy and chronotropy.

Nicotinic actions in SNS cause vasoconstriction, increased inotropy and chronotropy.

Front 15

MOA of carbachol:

Back 15

ACh analogue that is resistant to acetylcholinesterases (lasts longer).

It is non-selective.

Front 16

What is the therapeutic used of carbachol?

Back 16

It is rarely used, except as a 2nd/3rd line agent for open-angle glaucoma.

Decreases IOP.

Front 17

MOA of Bethanechol:

Back 17

ACh analogue that is resistant to acetylcholinesterases (lasts longer)

Selective for muscarinic receptors

Affects GI and urinary tracts when taken orally

Front 18

Therapeutic use of bethanechol?

Back 18

1. Urinary retention (e.g. post partum patients unable to urinate)

2. Gastroesophageal reflux (speeds gastric emptying)

Front 19

MOA of pilocarpine:

Back 19

Naturally occuring alkaloid that acts as ACh analogue.

Is longer acting and predominantly muscarinic.

Front 20

Therapeutic uses of pilocarpine?

Back 20

1. Treats open-angle glaucoma (lowers IOP)

2. Treats xerostomia (oral dryness), especially for cancer patients after chemo, or sjogren's syndrome.

Front 21

Of the muscarinic receptor subtypes, which are presynaptic and which are post synaptic?

Back 21

Post-synaptic: M1, M3, M5

Pre-synaptic: M2, M4

Front 22

Of the muscarinic receptor subtypes, which are stimulatory and which are inhibitor?

Back 22

Stimulatory: M1, M3, M5

Inhibitory: M2, M4

Front 23

Where is the M1 subtype located? (3)

Back 23

1. Parasympathetic ganglia

2. Salivary gland

3. Stomach

Front 24

Which is the M2 subtype located?

Back 24

1. Heart

2. GI SM

3. Bladder SM

4. CNS

*SM = Smooth muscle

Front 25

Where is the M3 subtype located? (6)

Back 25

1. Bladder SM

2. Airway SM

3. GI SM

4. Eye

5. Salivary glands

6. Blood vessels (dilation through indirect NO release)

*SM = Smooth muscle

Front 26

Where is the M4 subtype located? (2)

Back 26

1. Prejunctional nerve endings (inhibits ANS transmission)

2. CNS

Front 27

What do you call a big pile of kittens?

Back 27

A meowtain.

Front 28

Where is the M5 subtype located?

Back 28

CNS

Front 29

Define: Sjogren's syndrome

Back 29

Predominantly in women.

Incurable autoimmune disease of mucous membranes (mouth, vagina, nasal, skin)

Front 30

MOA of cevimelin:

Back 30

Activates M1 and M3 receptors in salivary gland.

Increases salivation to combat sjogren's syndrome, but also causes nausea.

Front 31

Which side effect may appear with pilocarpine use (all muscarinic receptors) that is not seen as often in cevimelin (M1, M3)?

Back 31

Bradycardia (M2 - not activated by cevimelin)

Front 32

Which muscarinic receptors regulate salivation?

Back 32

M1 and M3

Front 33

How are acetylcholinesterase inhibitors used to treat Alzheimer's disease?

Back 33

Alzheimer's patients are consistently found to have damaged cholinergic pathways.

Cholinergic neurons (neurons releasing ACh) in the CNS are decreased in number and function, leading to cognitive impairment.

Acetylcholinesterase inhibitors prevent the breakdown of ACh.

Front 34

Which acetylcholinesterase inhibitors can cross the blood brain barrier for the treatment of Alzheimer's disease? (3)

Back 34

1. Donepezil

2. Rivastigmine

3. Galantamine

Front 35

Aside from treatment of diseases, what other application is there for acetylcholinesterases?

Back 35

They can also be used as insecticides (ex. parathion, diazion, malathion, propoxur). However these are poisonous and not environmentally friendly.

Front 36

During cholinergic crisis, diarrhea may occur.

Which 1. nervous system (PNS/ SNS/ other) and 2. receptor (muscarinic/ nicotinic/ other) are affected?

Back 36

1. PNS

2. Muscarinic

Front 37

During cholinergic crisis, excitation may occur.

Which 1. nervous system (PNS/ SNS/ other) and 2. receptor (muscarinic/ nicotinic/ other) are affected?

Back 37

1. Other

2. Nicotinic

Front 38

During cholinergic crisis, sweating may occur.

Which 1. nervous system (PNS/ SNS/ other) and 2. receptor (muscarinic/ nicotinic/ other) are affected?

Back 38

1. SNS

2. Muscarinic

Front 39

During cholinergic crisis, muscle weakness may occur.

Which 1. nervous system (PNS/ SNS/ other) and 2. receptor (muscarinic/ nicotinic/ other) are affected?

Back 39

1. Other (muscles not part of ANS)

2. Nicotinic

Front 40

During cholinergic crisis, lacrimation may occur.

Which 1. nervous system (PNS/ SNS/ other) and 2. receptor (muscarinic/ nicotinic/ other) are affected?

Back 40

1. PNS

2. Muscarinic

Front 41

IV administered ACh causes hypotension and reflex tachycardia.

In contrast, IV pyridostigmine causes bradycardia and less predictably changes in BP.

Why?

Back 41

Acetylcholinesterase inhibitors act at ganglion of parasympathetic effector neuron and NMJ.

Unlike ACh, they do not affect vascular tone.

They can also affect sympathetic ganglion to increase cardiac output.